chr19-1206337-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000455.5(STK11):c.-577C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 229,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0020 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00055 ( 0 hom. )
Consequence
STK11
NM_000455.5 5_prime_UTR
NM_000455.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.436
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 19-1206337-C-T is Benign according to our data. Variant chr19-1206337-C-T is described in ClinVar as [Benign]. Clinvar id is 328209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00198 (299/151134) while in subpopulation AFR AF= 0.00695 (287/41296). AF 95% confidence interval is 0.00629. There are 1 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 299 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.-577C>T | 5_prime_UTR_variant | 1/10 | ENST00000326873.12 | NP_000446.1 | ||
STK11 | NM_001407255.1 | c.-577C>T | 5_prime_UTR_variant | 1/9 | NP_001394184.1 | |||
STK11 | NR_176325.1 | n.560C>T | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.-577C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_000455.5 | ENSP00000324856 | P1 | ||
STK11 | ENST00000585465.3 | c.-577C>T | 5_prime_UTR_variant | 1/10 | 5 | ENSP00000490268 | ||||
STK11 | ENST00000652231.1 | c.-577C>T | 5_prime_UTR_variant | 1/9 | ENSP00000498804 | |||||
STK11 | ENST00000585748.3 | c.-82-12080C>T | intron_variant | 3 | ENSP00000477641 |
Frequencies
GnomAD3 genomes AF: 0.00197 AC: 298AN: 151022Hom.: 1 Cov.: 31
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GnomAD4 exome AF: 0.000550 AC: 43AN: 78142Hom.: 0 Cov.: 0 AF XY: 0.000498 AC XY: 18AN XY: 36128
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GnomAD4 genome AF: 0.00198 AC: 299AN: 151134Hom.: 1 Cov.: 31 AF XY: 0.00196 AC XY: 145AN XY: 73848
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Peutz-Jeghers syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at